The review concluded that taxane-based doublet chemotherapy appeared to improve progression-free survival and partial response compared with single-agent taxane chemotherapy in patients with advanced breast cancer. As the review had several methodological and reporting flaws, the authors' conclusions may not be reliable.

To examine whether taxane-based doublet chemotherapy was effective compared with single-agent taxane in patients with advanced breast cancer and prior anthracycline treatment.

MEDLINE (to December 2009) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published in English; search terms were reported. Reference lists of identified articles were scanned. Trial investigators were asked to help to identify other studies.

Randomised controlled trials (RCTs) that compared taxane-based doublet with single-agent taxane chemotherapy in patients with advanced or metastatic breast cancer were eligible. Progression-free survival, overall response rate, and one year survival rate were the primary outcomes.

In the included trials, the age of participants ranged from 25 to 87 years. Doublet combinations varied, but half the studies used paclitaxel as a single agent with the other half using docetaxel. The included trials were published from 2002 to 2009. The authors reported that the trials were consistent in the way they defined progression-free survival.

The authors did not state how many reviewers selected studies.

The authors did not state that they evaluated study quality.

Intention-to-treat data were extracted (except for toxicity outcomes, where data were extracted for patients evaluable for toxicity) to calculate risk ratios (RR) with 95% confidence intervals (CI).

Two reviewers independently extracted the data, with disagreements resolved by discussion.

Meta-analyses were performed to calculate pooled risk ratios with 95% confidence intervals, using random-effects and fixed-effect models. Heterogeneity was assessed using the Q test.

Four RCTs were included with 2,207 patients (range 272 to 751).

A significant difference favouring taxane-based doublet over single-agent taxane chemotherapy was found for progression-free survival (RR 1.33, 95% CI 1.02 to 1.75; four trials with five intervention arms, the control arm of one trial was counted twice) and partial response (RR 1.43, 95% CI 1.10 to 1.86; two trials); the progression-free survival analysis was subject to significant statistical heterogeneity.

There were no statistically significant differences between chemotherapy regimens for overall response rate (four trials), one-year survival rate (two trials), clinical benefit (two trials), and complete response (two trials). Significant statistical heterogeneity was found for the overall response rate and complete response analyses.

Rates of (grade 3 and 4) neutropenia, nausea, fatigue, and alopecia did not differ significantly, but rates of stomatitis (RR 5.42, 95% CI 3.21 to 9.14; four trials) and diarrhoea (RR 2.51, 95% CI 1.53 to 4.12; four trials) were significantly higher with taxane-based doublet chemotherapy. Significant statistical heterogeneity was found for the neutropenia, fatigue, and alopecia analyses.

Taxane-based doublet chemotherapy appeared to improve progression-free survival and partial response compared with single-agent taxane chemotherapy in patients with advanced breast cancer.

The review addressed a clear question, supported by appropriate inclusion criteria. A basic search of two databases was conducted to identify studies, so the possibility of missed studies or language/publication bias affecting the review results could not be ruled out. Suitable methods were employed to reduce the risks of reviewer error and bias for the data extraction process, but such methods were not reported for the selection of studies for inclusion.

Trial quality was not appraised, so it was not possible to evaluate the reliability of the trial results. In addition, minimal patient characteristics were provided, which made it difficult to interpret individual trial results. Appropriate methods were used to assess heterogeneity, although sources of significant heterogeneity were not investigated. It was not always clear which type of model was used to calculate the pooled results presented.

As the review had several methodological and reporting flaws, the authors' conclusions may not be reliable.

Practice: The authors stated their results did not support the routine use of taxane-based doublet chemotherapy in clinical practice.

Research: The authors stated that there was an urgent need for RCTs in patients with metastatic breast cancer. Future trials that compare taxane-based doublet with single-agent regimen in anthracycline-pretreated patients with advanced breast cancer should be considered using adapted doses and schedules to obtain an effective and well-tolerated treatment.

Not stated.